A Novel MRI Tracer-Based Method for Measuring Water Diffusion in the Extracellular Space of the Rat Brain (December2013)

Abstract

We proposed a novel MRI tracer-based method for the determination of water diffusion in the brain extracellular space (ECS). The measuring system was validated in 32 Sprague Dawley rats. The rats were randomly divided into four groups with different injection sites: 1) caudate nucleus (Cn.); 2) thalamus (T.); 3) cortex (Cor.); and 4) substantia nigra (Sn.). The spin-lattice relaxation time of hydrogen nuclei in water molecules were shortened, which presented as high signal on MRI after the injection of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) into the rat brain ECS. The enhancement on MRI decreased over time due to the water diffusion and clearance process within the brain ECS. The process was dynamically recorded on a series of magnetic resonance (MR) images. As the increment in signal intensity (ΔSI) could be converted to local Gd-DTPA concentration, the water diffusion parameters were further calculated voxel by voxel based on a modified diffusion model. The most tortuous ECS (λ = 1.77 ± 0.71) was found in Sn. with D∗(Sn) of (2.06 ± 1.01) × 10(-4) mm(2)·s(-1) ( P < 0.05). No statistical difference was demonstrated among D∗(Cn), D∗(T.), and D∗(Cor). with an average D∗ values of (3.28 ± 0.88) × 10(-4) mm(2)·s(-1)( F = 0.18, P > 0.05). By using the tracer-based MRI method, the local diffusion parameters of the brain ECS can be quantitatively measured. The different distribution territories and clearance rates of the tracer in four brain areas indicated that the brain ECS is a physiologically partitioned system.

Altered Tracer Distribution and Clearance in the Extracellular Space of the Substantia Nigra in a Rodent Model of Parkinson's Disease

“…We found that Vd-max% of the SN was higher in the PD group than that of the other three groups, indicating that harmful substances such as α-syn were retained longer and distributed more widely in the PD model SN, increasing the likelihood of toxicity (Han et al, 2014; Ren et al, 2016). A previous study investigated tracer clearance in the normal rat SN ECS, but did not clearly establish clearance timesor diffusion ranges for the tracer (Han et al, 2014). Our study found that t 1/2 values were increased in the PD group compared to the other three groups, consistent with the above finding regarding Vd-max%.…”

“…Brain images were obtained with a high-resolution T1-weighted 3-dimensional magnetization-prepared rapid-acquisition with gradient echo (T1 3DMP-RAGE) sequence with the parameters specified by Han and Zuo (Han et al, 2014; Zuo et al, 2015). A 2-μl volume of 10 mmol/L Gd-DTPA solution (Magnevist; Bayer Schering Pharma AG, Berlin, Germany) was injected directly into the SN as described above (see Section Surgical Procedure).…”

“…Recently, MR imaging tracer-based methods such asgadolinium-diethylene triaminepentacetic acid (Gd-DTPA) have been applied to image the rat brain ECS (Han et al, 2014). Gd-DTPA was selected as a probe on the basis of its biomedical inertness, thermal stability, and relatively small molecular weight; additionally, Gd-DTPA primarily accumulates in the ECS without entering cerebral neurons (Han et al, 2014).…”

“…Gd-DTPA was selected as a probe on the basis of its biomedical inertness, thermal stability, and relatively small molecular weight; additionally, Gd-DTPA primarily accumulates in the ECS without entering cerebral neurons (Han et al, 2014). The use of Gd-DPTA as a MRI tracer not only allowed the visualization of dynamic brain clearance, but also the comprehensively measured for brain ECS diffusion parameters including the effective diffusion coefficient (D * ), clearance coefficient (k'), ratio of the maximum distribution volume of the tracer (Vd-max%), and half-life (t 1/2 ).…”

Peking University - Juntendo University Joint Symposium on Brain and Skin Diseases

“…IOI technology measures light signals generated by a fluorescent probe in ECS. Tracer-based MRI method uses magnetic sensitive contrast agents as a probe to tag and track water molecules in ISF 24) .…”